Zishen Huoxue decoction(ZSHX)alleviates ischemic myocardial injury(MI)via Sirt5-β-tubulin mediated synergistic mechanism of"mitophagy-unfolded protein response"and mitophagy  

作　　者：Xing Chang Siyuan Zhou Yu Huang Jinfeng Liu Yanli Wang Xuanke Guan Qiaomin Wu Zhiming Liu Ruxiu Liu 

机构地区：[1]Guang’anmen Hospital,China Academy of Chinese Medical Sciences,Beijing,100053

出　　处：《Chinese Journal of Natural Medicines》2025年第3期311-321,共11页中国天然药物(英文版)

基　　金：supported by the National Natural Science Foundation of China(No.82305204),the Special Project on Academic Inheritance and Communication,China Academy of Chinese Medical Sciences(No.CI2022E012XB);Chinese Academy of Chinese Medical Sciences Doctoral Talents Training Fund(No.2021);the Special Program for Training Outstanding Young Talents of Chinese Academy of Traditional Chinese Medicine(No.ZZ16-YQ-021);the Innovative Cultivation Project of Guang'anmen Hospital,Chinese Academy of Chinese Medical Sciences(No.2022s481).

摘　　要：Zishen Huoxue decoction(ZSHX)enhances cardiomyocyte viability following hypoxic stress;however,its upstream therapeutic targets remain unclear.Network pharmacology and RNA sequencing analyses revealed that ZSHX target genes were closely associated with mitophagy and apoptosis in the mitochondrial pathway.In vitro,ZSHX inhibited pathological mitochondrial fission following hypoxic stress,regulated FUN14 domain-containing protein 1(FUNDC1)-related mitophagy,and increased the levels of mitophagy lysosomes and microtubule-associated protein 1 light chain 3 beta II(LC3II)/translocase of outer mitochondrial membrane 20(TOM20)expression while inhibiting the over-activated mitochondrial unfolded protein response.Additionally,ZSHX regulated the stability of beta-tubulin through Sirtuin 5(SIRT5)and could modulate FUNDC1-related synergistic mechanisms of mitophagy and unfolded protein response in the mitochondria(UPR^(mt))via the SIRT5 and-β-tubulin axis.This targeting pathway may be crucial for cardiomyocytes to resist hypoxia.Collectively,these findings suggest that ZSHX can protect against cardiomyocyte injury via the SIRT5-β-tubulin axis,which may be associated with the synergistic protective mechanism of SIRT5-β-tubulin axis-related mitophagy and UPR^(mt) on cardiomyocytes.

关 键 词：MITOPHAGY Mitochondrial unfolded protein response Zishen Huoxue decoction Sirtuin 5 Β-TUBULIN Mitochondrial oxidative stress 

分 类 号：R73[医药卫生—肿瘤]